Diabetic nephropathy (DN) is a kidney disease that is a severe late complication of type 1 diabetes (T1D), which frequently requires renal replacement therapy. The primary diagnostic test to identify patients with T1D at risk for progressive renal dysfunction leading to DN has been microalbuminuria (MA) (1, 2). However, the predictive value of MA is now questioned: First, only a fifth of patients with MA will progress to proteinuria (3); second, a large proportion of patients with MA can revert to normoalbuminuria (4-6); and third, many patients at the onset of MA have begun to experience early renal function decline (ERFD) (7, 8). These findings have called into question the previous paradigm of DN in T1D, in which the finding of MA conveyed a high risk of progressive renal dysfunction and support a new model in which a subset of those with MA develop progressive ERFD. This change in our understanding of diabetic renal disease also is indicative of our incomplete understanding of the mechanisms of ERFD, a process that takes place while measured renal function is still in the normal or even elevated range. These findings emphasize the need for the development of biomarkers to diagnose kidney disease such as ERFD in those with MA.
Accordingly, there is an unmet need for new biomarkers and methods of using same for diagnosing kidney disease.